Original Article
Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model Cai‑Jun Wu, Zhi-Jun Guo, Chun‑Sheng Li, Yi Zhang, Jun Yang Department of Emergency, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, China
Abstract Background: Animal models of asphyxiation cardiac arrest (ACA) are frequently used in basic research to mirror the clinical course of cardiac arrest (CA). The rates of the return of spontaneous circulation (ROSC) in ACA animal models are lower than those from studies that have utilized ventricular fibrillation (VF) animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods: Forty‑eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation (CPR), defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area (AMSA) from the beginning of CPR and the pH at the beginning of CPR. A receiver‑operating characteristic (ROC) curve was used to evaluate the predictive value of AMSA for ROSC. Results: ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC (95% confidence intervals: 0.773∼0.983), and the optimum cut‑off value was 15.62 (specificity 95.7% and sensitivity 80.0%). Conclusions: The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model. Key words: Asphyxia; Cardiac Arrest; Cardiopulmonary Resuscitation; Logistic Regression Analyses; Return of Spontaneous Circulation
Introduction Modern cardiopulmonary resuscitation (CPR) has been performed for more than 50 years and is the most effective treatment for cardiac arrest (CA); however, CPR yields a functional survival rate of only 1.4–5.0%.[1,2] Insights into the pathophysiological processes of CA and postresuscitation syndrome have at least partially been gained from animal studies. It is generally accepted that results from animal models that more closely resemble human diseases can more reliably be extrapolated to humans. Asphyxiation CA (ACA) is one of the most prevalent causes of sudden cardiac death, and animal models of CA are thus frequently used in basic research to more closely mirror the clinical course of CA and CPR.[3‑5] However, in CPR studies that are based on the ACA animal models, the rates of the return of spontaneous circulation (ROSC) are Access this article online Quick Response Code:
Website: www.cmj.org
DOI: 10.4103/0366-6999.155106
1096
lower than those from studies that have utilized ventricular fibrillation (VF) CA models even under experimental conditions, including the type of animal used and the time for which CA goes untreated, that are identical.[3,5‑7] The CA criterion used in asphyxiation is blood pressure, and no other indexes are used.[3,5] Once ACA is achieved, CPR is performed homogeneously according to the guidelines. Every experimental life is cherished, and any anthropogenic factor that might affect the survival of the animals should be eliminated. Building on our previous studies, the purpose of this study was to characterize some of the pre‑CPR factors that are associated with ROSC in the ACA porcine model.[5] Our previous study demonstrated that three types of arrhythmias (i.e., VF, pulseless electrical activity [PEA], and asystole) occur with 8 min of untreated CA in ACA animal models.[5] The amplitude spectrum area (AMSA) has been reported to be useful in predicting the likelihood of successful defibrillation[8] and might be an index for predicting the likelihood of ROSC in VF CA animal Address for correspondence: Dr. Chun‑Sheng Li, Department of Emergency, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, China E‑Mail: [email protected]
Chinese Medical Journal ¦ April 20, 2015 ¦ Volume 128 ¦ Issue 8
models.[6] No studies have tested the ability of AMSA to predict the likelihood of ROSC in the ACA animal model. In the present study, we chose to examine the ability of AMSA to predict ROSC in the ACA animal model.
Methods Preparation of the animals
This prospective animal study was conducted with the approval of the Animal Care and Use Committee of Beijing Chao-Yang Hospital, affiliated with the Capital Medical University. The study was performed according to Utstein‑style guidelines[9] on 48 healthy Wu Zhishan inbred miniature pigs of both sexes aged 6–8 months and weighing 20 ± 2 kg. Initial sedation in each animal was achieved via intramuscular injection of ketamine (10 mg/kg) followed by ear vein injection of propofol (1.0 mg/kg). The anesthetized animals were intubated with 6.5‑mm cuffed endotracheal tubes via direct laryngoscopy. Propofol (1.0 mg/kg) and fentanyl (4 µg/kg) were then intravenously administered to reach the desired depth of anesthesia and analgesia, and 9 mg·kg-1·h-1 propofol and 1 µg·kg−1·h−1 (iv) fentanyl were subsequently used to maintain the anesthesia level. Additional doses of these drugs were administered when the heart rate exceeded 120 beats per min (BPM) and/or the systolic blood pressure exceeded 120 mmHg. The animals were mechanically ventilated with a volume‑controlled ventilator (Servo 900c; Siemens, Berlin, Germany) at a tidal volume of 8 ml/kg and a respiratory frequency of 12/min with room air. End‑tidal PCO2 was monitored with an in‑line infrared capnography system (CO2SMOplus monitor; Respironics Inc., Murrysville, PA, USA). The respiratory frequency was adjusted to maintain an end‑tidal PCO2 between 35 mmHg and 40 mmHg. Aortic pressure was measured with a fluid‑filled catheter advanced from the left femoral artery into the thoracic aorta. A Swan‑Ganz catheter (7F; Edwards Life Sciences, Irvine, CA, USA) was advanced from the left femoral vein and flow‑directed into the pulmonary artery to collect mixed venous blood. The catheter was calibrated before use, and its tip position was confirmed by the presence of characteristic pressure traces. An electrocardiograph was continuously recorded with a multichannel physiological recorder (BL‑420F Data Acquisition and Analysis System; Chengdu TME Technology Co. Ltd., Sichuan, China). All hemodynamic parameters were monitored with a multi‑function monitor (M1165; Hewlett‑Packard Co, Palo Alto, CA, USA).
Experimental protocols
After surgery, the animals were allowed to equilibrate for 60 min to achieve a stable resting level, and baseline data were then collected. The animals were paralyzed with 0.2 mg/kg cisatracurium to avoid gasping, and CA was then induced by clamping the endotracheal tube. The animals were asphyxiated until simulated pulselessness, defined as an aortic systolic pressure
Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model Cai‑Jun Wu, Zhi-Jun Guo, Chun‑Sheng Li, Yi Zhang, Jun Yang Department of Emergency, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, China
Abstract Background: Animal models of asphyxiation cardiac arrest (ACA) are frequently used in basic research to mirror the clinical course of cardiac arrest (CA). The rates of the return of spontaneous circulation (ROSC) in ACA animal models are lower than those from studies that have utilized ventricular fibrillation (VF) animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods: Forty‑eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation (CPR), defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area (AMSA) from the beginning of CPR and the pH at the beginning of CPR. A receiver‑operating characteristic (ROC) curve was used to evaluate the predictive value of AMSA for ROSC. Results: ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC (95% confidence intervals: 0.773∼0.983), and the optimum cut‑off value was 15.62 (specificity 95.7% and sensitivity 80.0%). Conclusions: The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model. Key words: Asphyxia; Cardiac Arrest; Cardiopulmonary Resuscitation; Logistic Regression Analyses; Return of Spontaneous Circulation
Introduction Modern cardiopulmonary resuscitation (CPR) has been performed for more than 50 years and is the most effective treatment for cardiac arrest (CA); however, CPR yields a functional survival rate of only 1.4–5.0%.[1,2] Insights into the pathophysiological processes of CA and postresuscitation syndrome have at least partially been gained from animal studies. It is generally accepted that results from animal models that more closely resemble human diseases can more reliably be extrapolated to humans. Asphyxiation CA (ACA) is one of the most prevalent causes of sudden cardiac death, and animal models of CA are thus frequently used in basic research to more closely mirror the clinical course of CA and CPR.[3‑5] However, in CPR studies that are based on the ACA animal models, the rates of the return of spontaneous circulation (ROSC) are Access this article online Quick Response Code:
Website: www.cmj.org
DOI: 10.4103/0366-6999.155106
1096
lower than those from studies that have utilized ventricular fibrillation (VF) CA models even under experimental conditions, including the type of animal used and the time for which CA goes untreated, that are identical.[3,5‑7] The CA criterion used in asphyxiation is blood pressure, and no other indexes are used.[3,5] Once ACA is achieved, CPR is performed homogeneously according to the guidelines. Every experimental life is cherished, and any anthropogenic factor that might affect the survival of the animals should be eliminated. Building on our previous studies, the purpose of this study was to characterize some of the pre‑CPR factors that are associated with ROSC in the ACA porcine model.[5] Our previous study demonstrated that three types of arrhythmias (i.e., VF, pulseless electrical activity [PEA], and asystole) occur with 8 min of untreated CA in ACA animal models.[5] The amplitude spectrum area (AMSA) has been reported to be useful in predicting the likelihood of successful defibrillation[8] and might be an index for predicting the likelihood of ROSC in VF CA animal Address for correspondence: Dr. Chun‑Sheng Li, Department of Emergency, Beijing Chao‑Yang Hospital, Capital Medical University, Beijing 100020, China E‑Mail: [email protected]
Chinese Medical Journal ¦ April 20, 2015 ¦ Volume 128 ¦ Issue 8
models.[6] No studies have tested the ability of AMSA to predict the likelihood of ROSC in the ACA animal model. In the present study, we chose to examine the ability of AMSA to predict ROSC in the ACA animal model.
Methods Preparation of the animals
This prospective animal study was conducted with the approval of the Animal Care and Use Committee of Beijing Chao-Yang Hospital, affiliated with the Capital Medical University. The study was performed according to Utstein‑style guidelines[9] on 48 healthy Wu Zhishan inbred miniature pigs of both sexes aged 6–8 months and weighing 20 ± 2 kg. Initial sedation in each animal was achieved via intramuscular injection of ketamine (10 mg/kg) followed by ear vein injection of propofol (1.0 mg/kg). The anesthetized animals were intubated with 6.5‑mm cuffed endotracheal tubes via direct laryngoscopy. Propofol (1.0 mg/kg) and fentanyl (4 µg/kg) were then intravenously administered to reach the desired depth of anesthesia and analgesia, and 9 mg·kg-1·h-1 propofol and 1 µg·kg−1·h−1 (iv) fentanyl were subsequently used to maintain the anesthesia level. Additional doses of these drugs were administered when the heart rate exceeded 120 beats per min (BPM) and/or the systolic blood pressure exceeded 120 mmHg. The animals were mechanically ventilated with a volume‑controlled ventilator (Servo 900c; Siemens, Berlin, Germany) at a tidal volume of 8 ml/kg and a respiratory frequency of 12/min with room air. End‑tidal PCO2 was monitored with an in‑line infrared capnography system (CO2SMOplus monitor; Respironics Inc., Murrysville, PA, USA). The respiratory frequency was adjusted to maintain an end‑tidal PCO2 between 35 mmHg and 40 mmHg. Aortic pressure was measured with a fluid‑filled catheter advanced from the left femoral artery into the thoracic aorta. A Swan‑Ganz catheter (7F; Edwards Life Sciences, Irvine, CA, USA) was advanced from the left femoral vein and flow‑directed into the pulmonary artery to collect mixed venous blood. The catheter was calibrated before use, and its tip position was confirmed by the presence of characteristic pressure traces. An electrocardiograph was continuously recorded with a multichannel physiological recorder (BL‑420F Data Acquisition and Analysis System; Chengdu TME Technology Co. Ltd., Sichuan, China). All hemodynamic parameters were monitored with a multi‑function monitor (M1165; Hewlett‑Packard Co, Palo Alto, CA, USA).
Experimental protocols
After surgery, the animals were allowed to equilibrate for 60 min to achieve a stable resting level, and baseline data were then collected. The animals were paralyzed with 0.2 mg/kg cisatracurium to avoid gasping, and CA was then induced by clamping the endotracheal tube. The animals were asphyxiated until simulated pulselessness, defined as an aortic systolic pressure
